Clinical and immunological outcomes of rituximab-based, mycophenolate mofetil-based and cyclophosphamide-based treatment strategies for systemic lupus erythematosus with active kidney involvement from LOOPS registry.

OBJECTIVES: To evaluate the clinical outcomes and explore longitudinal peripheral blood immunophenotypic changes associated with rituximab (RTX)-based, mycophenolate mofetil (MMF)-based or intravenous cyclophosphamide (IVCY)-based treatment strategies for patients with systemic lupus erythematosus (SLE) and active lupus nephritis. METHODS: We retrospectively analysed patients with SLE and active lupus nephritis enrolled in the LOOPS registry who received single-agent induction therapy with RTX, MMF or IVCY in addition to glucocorticoids (GCs). The co-primary endpoints were the achievement rates of complete renal response (CRR) and urinary protein-to-creatinine ratio <0.7 g/gCr at week 52. Secondary endpoints included renal function, proteinuria, disease activity, relapse rate and safety. Peripheral blood immune cell subsets were assessed by multicolour flow cytometry before and after treatment. RESULTS: At week 52, no significant differences were observed in CRR rates or improvement in proteinuria among the groups. Changes in estimated glomerular filtration rate, disease activity measures and concomitant GC dose also did not differ significantly. Exploratory within-strategy analyses showed reduced B-cell subset proportions with RTX and broader reductions, including in activated T cells, with MMF and IVCY. However, treatment strategy-by-time interaction was not significant, providing no evidence of between-strategy differences in longitudinal changes. CONCLUSION: The 52-week clinical effectiveness of the RTX-based, MMF-based and IVCY-based strategies for active lupus nephritis did not differ significantly. Different within-strategy immunophenotypic patterns were observed, but between-strategy differences were not confirmed. Comprehensive immunophenotyping may help characterise immune dynamics and support future response stratification and precision medicine for lupus nephritis.